The field of the invention relates to methods for treating and/or preventing cell proliferation diseases and disorders such as cancer. In particular, the field of the invention relates to methods for treating and/or preventing breast cancer and/or ductal carcinoma in situ (DCIS) that include administering a topical formulation of the tamoxifen metabolite N-desmethyl-4-hydroxytamoxifen, otherwise called endoxifen.
Despite large Phase III clinical trials that have established the success of selective estrogen receptor modulators (SERMs) for breast cancer prevention and therapy of duct carcinoma in situ (DCIS), uptake of SERMS by women with these problems has been poor. (Lee et. al., Local transdermal therapy to the breast for breast cancer prevention and DCIS therapy: preclinical and clinical evaluation. Cancer Chemother Pharmacol. 2015. November; Epub ahead of print. PMID: 26560487 and Lee et. al., Novel routes for administering chemoprevention: Local transdermal therapy to the breasts. Semin Onc. 2016 February; 43(1):107-15. PMID: 26970129). Reasons include quality of life impairments, the possibility of serious side effects, and reluctance by healthy women to take oral medication for prevention. However, breast cancer prevention requires only that the breast be exposed to the drug; systemic exposure is both unnecessary and harmful. For example, 5 years of systemic exposure with oral TAM leads to benefits to the breast and bone, but with costs to quality of life, and health. An alternative to oral delivery is that of transdermal delivery of drugs through the breast skin; its advantages include low systemic exposure, the avoidance of fast hepatic metabolism, and simplicity of application which will allow dissemination across the globe. Therefore, local transdermal therapy (LTT) to the breast is likely to improve the tolerability and the acceptance of pharmacological cancer prevention regimens by women. Consequently, we have introduced the concept of transdermal delivery of SERMs for breast cancer prevention and DCIS therapy (see Lee et al. A randomized phase II presurgical trial of transdermal 4-Hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast. Clinical Cancer Res, 2014 Jul. 15; 20(14):3672-82. doi: 10.1158/1078-0432.CCR-13-3045 and Lee et. al., Local transdermal therapy to the breast for breast cancer prevention and DCIS therapy: preclinical and clinical evaluation. Cancer Chemother Pharmacol. 2015. November; Epub ahead of print. PMID: 26560487 and Lee et. al., Novel routes for administering chemoprevention: Local transdermal therapy to the breasts. Semin Onc. 2016 February; 43(1):107-15. PMID: 26970129).